ClinVar Miner

Submissions for variant NM_000096.4(CP):c.2756T>C (p.Leu919Pro)

dbSNP: rs1135401784
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Hemoglobin and Genome Lab, University of Campinas RCV000496150 SCV000586733 likely pathogenic Deficiency of ferroxidase 2017-07-28 criteria provided, single submitter research
Mendelics RCV000496150 SCV002519432 pathogenic Deficiency of ferroxidase 2022-05-04 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003226310 SCV003922500 likely pathogenic Neurodegeneration with brain iron accumulation 2023-03-10 criteria provided, single submitter clinical testing Variant summary: CP c.2756T>C (p.Leu919Pro) results in a non-conservative amino acid change in the encoded protein sequence. Four of four in-silico tools predict a damaging effect of the variant on protein function. At least one computational study showed Leu919 is involved in a network of hydrophobic interactions with Leu921 and Leu808 and the substitution by a proline would probably lead to perturbations in this network, altering the stability of the protein (Vila Cuenca_2020). The variant was absent in 251254 control chromosomes (gnomAD). c.2756T>C has been reported in the literature in homozygous individuals affected with Aceruloplasminaemia (Borges_2019, Vila Cuenca_2020) and one heterozygote carrier whose serum ceruloplasmin levels were decreased, with normal ferritin and serum iron (Borges_2019). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters (evaluation after 2014) cite this variant as pathogenic and likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.